Although human alveolar epithelium has long been known to be permeable to insulin, actual diabetes management by insulin administration via lung awaited development of a practical delivery system. A new dry powder insulin formulation and aerosol delivery device permits reproducible pulmonary delivery of rapid-acting insulin in therapeutic amounts with 1-2 inhalations per dose. To compare safety and efficacy of a regimen using this inhaled insulin (INH) vs. a conventional injection regimen, 70 patients with type 1 diabetes mellitus from 10 study sites were randomized, after a 1 month run-in period, to either inhaled or subcutaneous insulin (n=35 each) treatment for 3 months. Subcutaneous continued their pre-study insulin regimen (2-3 injections/day), while inhaled insulin was administered pre-meals plus Ultralente insulin injection at bedtime. Home blood sugar monitoring was performed 4 times daily and was reviewed weekly. Insulin was adjusted to target premeal glucose 100-160 mg/dl.